Low Cardiorespiratory Fitness Research Articles

Left Ventricular Volume as a Predictor of Exercise Capacity and Functional Independence in Individuals with Normal Ejection Fraction.

Low cardiorespiratory fitness (CRF) is associated with functional disability, heart failure and mortality. Left ventricular (LV) end-diastolic volume (LVEDV) has been linked with CRF, but its utility as a diagnostic marker of low CRF has not been tested. This multi-center international cohort examined the relationship between LV size on echocardiography and CRF (peak oxygen uptake [peak VO2] from cardiopulmonary exercise testing) in individuals with LV ejection fraction ≥50%. Absolute and BSA-indexed LVEDV (LVEDVi) were tested as predictors of low CRF and functional disability (peak VO2 <1100ml/min or <18 ml/kg/min) and compared against candidate measures of cardiac structure and function. 2876 individuals (309 endurance athletes, 251 healthy non-athletes, 1969 individuals with unexplained dyspnea, 347 individuals with heart failure with preserved ejection fraction) were included. For the entire cohort, LVEDV had the strongest univariable association with peak VO2 (R2 =0.45, standardized [std]β 0.67, p<0.001) and remained the strongest independent predictor of peak VO2 after adjusting for age, sex and BMI (stdβ 0.30, p<0.001). LVEDV was better at identifying low CRF than most established echocardiographic measures (LVEDV AUC 0.72; LVEDVi AUC 0.71), but equivalent to the E/e' ratio. The probability of achieving a peak VO2 below the functional independence threshold was highest for smaller ventricular volumes, with LVEDV and LVEDVi of 88ml and 57ml/m2 providing the optimal cut-points, respectively. Small resting ventricular size is associated with a higher probability of low CRF and functional disability. LV size is the strongest independent echocardiographic predictor of CRF across the health-disease continuum.

Coexistence of obesity and unhealthy cardiorespiratory fitness in a cohort of boys.

The aim of the present study was to examine: 1) the coexistence of excessive body weight and low cardiorespiratory fitness (CRF), at a level to be considered unhealthy, and 2) the stability (tracking) of this profile. 1754 European boys, aged 8- to 14-years old, were tested for CRF and based on international cut points were classified as having healthy (H) or unhealthy (UN) CRF. Based on BMI they were classified as having normal weight (N), or overweight or obesity (OO). Chi-square was performed with four groups (i.e. N/H, N/UN, OO/H and OO/UN) and the odds ratios were calculated (cross-sectional analysis). A sub-group of 353 boys were followed for an average of 3.79±0.83 years (range: 2.97-6.06; longitudinal analysis). The odds that a boy was with OO/UN profile compared to the normal body weight category ranged from 2.67 (13-years old) to 6.74 (9-years old). 56.6% of the participants remained in the same category, whereas 28.0% of them had ≥1 change in category to worst in the second assessment (Cohen Kappa= 0.557, p<0.001; substantial agreement). The odds ratios of having boys with unhealthy profile of combined excessive body weight and low CRF ranged from medium to large. The stability of unhealthy profile was substantial.

Left ventricular volume as a predictor of exercise capacity and functional independence in individuals with preserved ejection fraction

Abstract Background Cardiorespiratory fitness (CRF) is vital for independent living and is a powerful prognostic marker. Increased left ventricular (LV) volume has been linked with high CRF in athletes, but its utility as a diagnostic marker of low CRF across the entire health-disease continuum has yet to be tested. Methods This multi-center international cohort from Australia and Belgium examined the relationship between ventricular size on resting echocardiography and CRF (peakVO2 from cardiopulmonary exercise testing [CPET] or CPET with simultaneous echocardiography) in individuals with preserved LV ejection fraction (≥50%). LV end-diastolic volume (LVEDV) and LVEDV indexed to body surface area (LVEDVi) were tested as predictors of very low CRF (CRF associated with functional disability - peakVO2 &amp;lt; 1100ml or &amp;lt;18 ml/kg/min) and compared against other candidate measures of systolic and diastolic cardiac function that have been associated with heart disease. Thresholds for absolute and indexed LVEDV which best distinguished between lower and higher CRF status were identified. Results 2876 individuals (251 healthy non-athletes, 309 elite endurance athletes, 1969 individuals with unexplained dyspnea, 347 individuals with heart failure with preserved ejection fraction) were included. For the entire cohort, LVEDV had the strongest univariate association with peakVO2 (R2 = 0.45, standardized [std] β 0.67, p&amp;lt; 0.001) and, remained the strongest independent predictor of peakVO2 after adjusting for age, sex and body mass index (std β 0.44, p &amp;lt; 0.001). The relationship between LVEDV and VO2peak differed based on health/disease status (Figure 1). LVEDV demonstrated the greatest diagnostic capability in identifying functional disability (LVEDV AUC 0.72; LVEDVi AUC 0.71, Figure 2), outperforming ejection fraction, diastolic velocities, atrial volumes and pulmonary artery pressure estimates. The probability of achieving a peak VO2 below the threshold required for functional independence was highest for smaller ventricular volumes with LVEDV and LVEDVi of 88ml and 57 ml/m2 proving the optimal cut-points, respectively. Conclusions A small LVEDV is associated with a higher probability of poor exercise capacity, failure to achieve the peak VO2 required for functional independence and is the strongest independent echocardiographic predictor of CRF across the health-disease continuum.Figure 1.Ventricular Size and CRFFigure 2.Predictors of CRF status

Does greater adherence to a healthy dietary pattern correspond to a better body composition and cardiorespiratory fitness in adults with overweight and primary hypertension? Data from the EXERDIET-HTA study.

Cardiovascular events are positively associated with primary hypertension (HTN), obesity, and low cardiorespiratory fitness (CRF) and negatively with healthy dietary patterns, such as Healthy Diet Indicator (HDI), Mediterranean diet (MD), and the Dietary Approaches to Stop Hypertension (DASH). The aim is to analyze the association between healthy dietary patterns with body composition and CRF. Body composition (bioimpedance) and CRF [peak oxygen uptake (V̇O2peak)] were assessed in 165 participants with HTN and overweight/obesity. There were (1) a positive association (unadjusted) between fat-free mass (%) with DASH and MD (P = 0.03) and a negative association between fat mass (%) and MD (P = 0.03); (2) positive associations (adjusted) between V̇O2peak (l·min-1) with DASH (P = 0.007), HDI (P = 0.017), and MD (P = 0.010) and V̇O2peak (ml·kg-1·min-1) with DASH (P = 0.005); (3) a negative relationship (unadjusted and adjusted) between energy intake and DASH (P = 0.004). In conclusion, these findings highlight the cardiovascular health protection provided by healthy dietary patterns associated with healthier CRF and body composition in people with a profile of HTN and overweight.

Reallocation of time to moderate-to-vigorous physical activity and estimated changes in physical fitness among preschoolers: a compositional data analysis

BackgroundPrevious research has examined the associations of preschoolers’ 24-h movement behaviours, including light and moderate-to-vigorous physical activity (LPA and MVPA), sedentary behaviour (SB), sleep, with physical fitness in isolation, ignoring intrinsically compositional nature of movement data while increasing the risk of collinearity. Thus, this study investigated the associations of preschoolers’ 24-h Movement behaviours composition with physical fitness, estimated changes in physical fitness when time was reallocated between movement behaviours composition, and determined whether associations differ between different genders, using compositional data analysis.MethodsIn the cross-sectional study, a total of 275 preschoolers (3 ~ 6 y) from China were included. SB, LPA and MVPA times were objectively monitored with an ActiGraph GT9X accelerometer for 7 consecutive days. Sleep duration was obtained using parental reports. Physical fitness parameters, including upper and lower limb strength, static balance, speed-agility, and cardiorespiratory fitness (CRF), were determined with the PREFIT battery. The associations of 24-h movement behaviours composition with each physical fitness parameter were examined employing compositional multivariable linear regression models. The changes following time reallocation among behaviours were estimated employing compositional isotemporal substitution analyses.ResultsGreater MVPA, but not LPA, was significantly related to better upper and lower limb strength, speed-agility, and CRF. Reallocating time from LPA or SB to MVPA was related to better physical fitness. The associations were non-symmetrical: the estimated detriments to physical fitness from replacing MVPA with LPA or SB were larger than the estimated benefits associated with adding MVPA of the same magnitude. The aforementioned associations with lower limb strength, CRF, and speed-agility were observed in boys, while associations with upper and lower limb strength were noted in girls.ConclusionOur findings reinforce the importance of physical activity (PA) intensity for the development of physical fitness in preschoolers. Replacing LPA or SB time with MVPA may be an appropriate strategy for enhancing preschoolers’ physical fitness.

Stair climbing and risk of incident atrial fibrillation: Effect modulated by sex, genetic predisposition, and cardiorespiratory fitness

Background and aimsStair climbing, a straightforward and impactful form of physical activity, has shown potential in reducing risks of cardiovascular disease and mortality. However, its association with the development of atrial fibrillation (AF) remains largely unexplored. Methods and results451,089 participants (mean age 56.5 years) without cardiovascular disease (year 2006–2010) were included from the UK Biobank study. Stair climbing data was collected through touchscreen questionnaire. AF cases were identified using ICD-10 code: I48 and were followed until February 1, 2022. Models adjusted for traditional cardiovascular risk factors. Over a median follow-up of 12.6 years, 23,660 (5.2 %) participants experienced new-onset AF. In multivariable-adjusted models, climbing 10–50, 60–100, 110–150, and ≥160 steps of stairs per day were associated with significant reductions in the risk of AF, compared to not climbing any stairs. The risk reduction appeared more pronounced in women than in men (P for interaction = 0.09). When compared to participants who climbed no stairs, the HRs for those who climbed 110–150 steps of stairs per day were 0.69 (95 % CI: 0.58–0.82) among those with low cardiorespiratory fitness, 0.71 (95 % CI: 0.57–0.88) among those with intermediate cardiorespiratory fitness, and 0.83 (95 % CI: 0.64–1.07) among those with high cardiorespiratory fitness. ConclusionsClimbing stairs was associated with a reduction in AF risks. Significant interaction between cardiorespiratory fitness and stair climbing associated with incident AF was observed. Findings suggest that promoting regular stair climbing could be a potential target for preventing AF onset.

Risk and determinants of sarcopenia in people with diabetes: a case–control study from Qatar Biobank cohort

BackgroundDiabetes is associated with impairments in muscle mass and quality increasing the risk of sarcopenia. Thus, this study aimed to investigate the odds of sarcopenia and its associated risk factors among Qatari adults (> 18 years), while exploring the modulating effects of health and lifestyle factors.MethodsUsing a case–control design, data from 767 participants (481 cases with diabetes and 286 controls without diabetes) was collected from Qatar Biobank (QBB). Sociodemographic, lifestyle factors including dietary intake, anthropometric and biochemical measures were analyzed. Handgrip strength, Dual X-ray absorptiometry (DXA), and Bio-impedance were used to assess muscle strength, muscle mass and muscle quality, respectively. The risk of sarcopenia was estimated using the European consensus on definition and diagnosis of sarcopenia.ResultsCases with diabetes were older (55 vs. 36 years; P < 0.001), had higher BMI (31.6 vs. 28.3 kg/m2; P < 0.001), lower cardiorespiratory fitness (50.0% “Moderate” fitness for cases, 62.9% “High” fitness for controls), and consumed less total (59.0 vs. 64.0; P = 0.004) and animal protein (39.0 vs. 42.0; P = 0.001), compared to controls based on a computed score. Participants with diabetes also had lower appendicular lean mass/BMI, handgrip strength, and higher probability of sarcopenia/probable sarcopenia (P < 0.005). Adjusted multiple logistic regression revealed that elevated cardiorespiratory fitness (β = 0.299, 95%CI:0.12–0.74) and blood triglycerides (β = 1.475, 95% CI: 1.024–2.124), as well as being a female (β = 0.086, 95%CI: 0.026–0.288) and having higher BMI (β = 0.908, 95%CI: 0.852–0.967) and ALM/BMI (β = 0.000, 95% CI: 0.000–0.007) are independent predictors (p < 0.05) of sarcopenia risk.ConclusionsThis study highlights the intricate relationship between diabetes and sarcopenia, revealing modifiable risk factors. Individuals with diabetes were found to have a higher likelihood of sarcopenia, which was associated with lower fitness levels and higher blood triglycerides. Protective factors against sarcopenia included being female and having higher BMI and ALM/BMI ratios.

Association Between Cardiorespiratory Fitness and Trend of Age-Related Rise in Arterial Stiffness in Individuals With and Without Hypertension or Diabetes

Abstract BACKGROUND This study aimed to investigate whether higher cardiorespiratory fitness (CRF) can modify the trend of age-related rise in arterial stiffness in individuals with and without hypertension (HTN) or diabetes. METHODS The study included 4,935 participants who underwent maximal cardiopulmonary exercise testing with respiratory gas analysis in a health screening program. CRF was directly measured using peak oxygen uptake during the cardiopulmonary exercise test, while arterial stiffness was evaluated using brachial–ankle pulse wave velocity (baPWV). RESULTS Participants with high CRF levels had significantly lower baPWV compared with those with low CRF levels, regardless of HTN or diabetes status (P &amp;lt; 0.05). The trend of baPWV increased with age, but the rate of age-related increase in baPWV was lower in individuals with moderate-to-high CRF levels compared with those with low CRF levels, regardless of HTN or diabetes status. Joint association analysis indicated that the trend of age-related increase in baPWV was the lowest in fit individuals without HTN or diabetes compared with unfit individuals with HTN or diabetes (P &amp;lt; 0.01). However, the trend of age-related increase in baPWV was not attenuated in fit with HTN or diabetes compared with unfit with HTN or diabetes. CONCLUSIONS These findings suggest that higher CRF levels may mitigate the trend of age-related rise in arterial stiffness in individuals with and without HTN or diabetes. However, this attenuating trend appears more pronounced in individuals without HTN or diabetes.

Poor stress resilience in adolescence predicts higher risk of severe COVID-19 and other respiratory infections: A prospective cohort study of 1.4 million Swedish men

ObjectivesTo investigate the associations between stress resilience in late adolescence and later risk of severe COVID-19 and other lower respiratory infections. A secondary aim was to examine potential confounding between low cardiorespiratory fitness (CRF) and stress resilience in relation to respiratory infection. MethodsWe conducted a registry-based cohort study of 1.4 million Swedish men, undergoing military conscription between 1968 and 2005. All were assessed by a psychologist for stress resilience, receiving a score between 1 and 9. The outcomes were hospitalization or death due to COVID-19 from March 2020 to September 2021 and hospitalization due to bacterial or viral pneumonia from conscription until January 2020. A secondary aim was to examine potential confounding between low cardiorespiratory fitness (CRF) and stress resilience in relation to respiratory infection. ResultsPoor stress resilience in late adolescence is associated with later risk of severe lower respiratory infections. Using a high resilience score as the reference, the hazard ratio (95 % CI) for death due to COVID-19 for the lowest scores was 1.49 (1.01–2.18) adjusted for CRF and other confounders. The corresponding adjusted hazard ratios for hospitalization due to bacterial pneumonia were 2.28 (2.03–2.57) and for viral pneumonia 1.92 (1.33–2.79). No significant interaction was seen between stress resilience and CRF in the analysis. ConclusionsPoor stress resilience is a prospective factor for severe COVID-19 as well as for bacterial and viral respiratory pneumonia endpoints, independent of CRF. These findings imply an effect of late adolescent stress resilience on the immune system later in life.

Visceral adiposity: A major mediator of the relationship between epicardial adiposity and cardiorespiratory fitness in adults

Background and aimsEpicardial adiposity has been positively associated with visceral adipose tissue (VAT). Few studies have examined the association between cardiorespiratory fitness (CRF) and epicardial adiposity. Furthermore, whether this relationship was independent of VAT remains unexplored. Our purpose was to investigate the contribution of VAT in the relationships between CRF, physical activity (PA) and epicardial adipose tissue (EAT) in asymptomatic women and men. Methods and resultsWe examined the associations between EAT and VAT measured by magnetic resonance imaging, CRF measured by cardiopulmonary exercise testing, and PA assessed using pedometers and a 3-day PA journal in 239 apparently healthy adults (43 % women). Participants were compared according to EAT tertiles and CRF level in both sexes. Participants with the highest EAT level presented more VAT (p < 0.001), lower CRF (p < 0.01), and a more deteriorated cardiometabolic health score (p < 0.01) than those with the lowest EAT level. CRF was negatively associated with EAT in both sexes (p < 0.01). No significant relationship was found with PA (p = NS). Stepwise multivariable regression analyses showed that VAT explained most of the variance in EAT in women and men. Mediation analyses confirmed that VAT was a mediator of the association between CRF and EAT in both sexes. ConclusionIn women and men, VAT appears as a major mediator of the association between CRF and EAT thereby suggesting that managing VAT by improving CRF could help in the prevention of cardiometabolic disorders related to excess EAT.

Physiological fitness in people with advanced multiple sclerosis

IntroductionPhysiological fitness, encompassing cardiorespiratory fitness (CRF) and body composition, are important markers of overall health, functional capacity, and quality of life in general and clinical populations. Characterizing fitness is important for the development of tailored interventions and strategies to optimize well-being across the spectrum of disability in multiple sclerosis (MS). While existing research has explored fitness in people with mild-to-moderate disability, there is a scarcity of data in people with advanced MS (Expanded Disability Severity Scale, EDSS≥7.0). ObjectiveTo characterize CRF and body composition and their associations with fatigue, quality of life, and function in individuals with advanced MS. MethodsParticipants (n=18, mean age=60.7 years-old, median EDSS=7.5) underwent a cardiopulmonary exercise test and dual-energy X-ray absorptiometry scanning. Main outcomes included peak volume of oxygen uptake (V̇O2peak) and whole and regional body fat, lean mass, bone mineral content, and bone density. Symptoms of fatigue (Modified Fatigue Impact Scale, MFIS), quality of life (29-item MS Impact Scale, MSIS-29), and daily function (Late-Life Function and Disability Instrument, LLFDI) were collected. ResultsParticipants exhibited notably low CRF levels (V̇O2peak=9.8 mL/min/kg) and poor body composition (lower lean mass, bone mineral content and density) compared to previous studies in the general population and in individuals with MS with lower disability. V̇O2peak was most consistently associated with function in daily life (LLFDI scores, rs≥0.637, p≤0.004). ConclusionThese findings reinforce the potential importance of physiological fitness to preserve function in people with advanced MS.

High-intensity interval training improves cardiovascular and physical health in patients with rheumatoid arthritis: a multicentre randomised controlled trial

ObjectivesPatients with rheumatoid arthritis (RA) have substantially elevated risk for cardiovascular diseases, and low cardiorespiratory fitness (VO2max) is a major mediator. The aim of this assessor-blinded, two-armed multicentre randomised controlled...

The Relationship of Cardiorespiratory Fitness, Physical Activity, and Coronary Artery Calcification to Cardiovascular Disease Events in CARDIA Participants.

Moderate-to-vigorous-intensity physical activity (MVPA), cardiorespiratory fitness (CRF), and coronary artery calcification (CAC) are associated with cardiovascular disease (CVD) risk. While a U-shaped relationship between CRF or MVPA and CAC has been reported, the presence of CAC among highly fit individuals might be benign. We examined interactive associations of CRF or MVPA and CAC with outcomes and evaluated the relationship of CRF and MVPA to CAC incidence. CARDIA participants with CAC assessed in 2005-06 were included (n=3,141, mean age 45). MVPA was assessed by self-report and accelerometer. CRF was estimated with a maximal graded exercise test. Adjudicated CVD events and mortality data were obtained through 2019. CAC was reassessed in 2010-11. Cox models were constructed to assess hazard ratios (HRs) for CVD, coronary heart disease (CHD), and mortality in groups defined by CAC presence/absence and lower/higher CRF or MVPA levels. Logistic models were constructed to assess associations with CAC incidence. Adjustment was made for sociodemographic and CVD risk factors. Relative to participants with no CAC and higher CRF, the adjusted HRs for CVD were 4.68 for CAC and higher CRF, 2.22 for no CAC and lower CRF, and 3.72 for CAC and lower CRF. For CHD, the respective HRs were 9.98, 2.28, and 5.52. For mortality, the HRs were 1.15, 1.58, and 3.14, respectively. Similar findings were observed when MVPA, measured either by self-report or accelerometer, was substituted for CRF. A robust inverse association of CRF and accelerometer-derived MVPA with CAC incidence was partly accounted for by adjusting for CVD risk factors. In middle-aged adults, CRF and MVPA demonstrated an inverse association with CAC incidence but did not mitigate the increased cardiovascular risk associated with CAC, indicating that CAC is not benign in individuals with higher CRF or MVPA levels.

The Interplay of Type 2 Diabetes Status, Cardiorespiratory Fitness Level, and Sudden Cardiac Death: A Prospective Cohort Study

BackgroundTo evaluate the individual and joint effects of type 2 diabetes (T2D) status and cardiorespiratory fitness (CRF) level with sudden cardiac death (SCD) risk. MethodsPrevalent T2D was defined based on guideline recommendations, and CRF level was assessed using a respiratory gas-exchange analyzer during exercise testing at baseline, in 2308 men aged 42-61 years. T2D status was classified as either “Yes” or “No,” and CRF level was classified as low, medium, or high. Cox regression analysis was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for SCD. ResultsA total of 264 SCDs occurred during a median follow-up of 28.1 years. Comparing Yes vs No history of T2D, the multivariable-adjusted HR (95% CI) for SCD was 1.79 (1.19-2.72). Comparing low vs high CRF levels, the corresponding adjusted HR (95% CI) for SCD was 1.77 (1.21-2.58). The HRs persisted when T2D status was further adjusted for CRF level, and vice versa. Compared with No-T2D & medium-high CRF level, men with No-T2D & low CRF and those with Yes-T2D & low CRF had an increased SCD risk: (HR = 1.87, 95% CI, 1.38-2.55) and (HR = 3.34, 95% CI, 2.00-5.57), respectively. No significant association occurred between men with Yes-T2D & medium-high CRF and SCD risk (HR = 1.46, 95% CI, 0.46-4.65). Modest evidence indicated the presence of additive and multiplicative interactions between T2D status and CRF level, in relation to SCD. ConclusionsAn interplay exists between T2D status, CRF level, and SCD risk in middle-aged and older men. Higher CRF levels may mitigate the increased SCD risk observed in men with T2D.

Cardiorespiratory fitness and body mass index on metabolic syndrome in middle-aged Japanese adults under national health guidance: a cross-sectional study

ObjectivesPoor cardiorespiratory fitness (CRF) and high body mass index (BMI) increased the risk of developing metabolic Syndrome (MetS) mostly in Caucasians. However, the sex-specific combined association of CRF and BMI on MetS considering health-related behaviors has yet to be thoroughly examined in Japanese. This study aims to investigate the sex-specific independent and combined associations of CRF and BMI with MetS in middle-aged Japanese adults.Methods421 participants were included in this cross-sectional study. CRF was estimated using a submaximal cycle ergometer. CRF and BMI were respectively divided into three categories according to tertile distribution. MetS was diagnosed based on five risk factors: waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression models were used to estimate independent and combined association of CRF and BMI with MetS.ResultsResults showed that 154 (57.5%) and 70 (45.8%) of men and women had MetS, respectively. Compared to men with lower CRF or higher BMI, men with middle and higher CRF or middle and lower BMI were less likely to have MetS. Compared with ‘unfit and higher BMI’ group, ‘unfit and lower BMI’, ‘fit and higher BMI’, and ‘fit and lower BMI’ groups in men showed statistically significant decreased prevalences of MetS. However, no significant associations were found in women.ConclusionsThis study found significant independent and combined associations of CRF and BMI with MetS only in men, but not in women. However, prospective studies are warranted to confirm sex-specific associations of CRF and BMI with MetS.

Left ventricular volume and maximal functional capacity in heart failure with preserved ejection fraction: Size matters.

Emerging evidence suggests that smaller left ventricular volumes may identify subjects with lower cardiorespiratory fitness. Whether left ventricular size predicts functional capacity in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. This study aimed to explore the association between indexed left ventricular end-diastolic volume (iLVEDV) and maximal functional capacity, assessed by peak oxygen consumption (peakVO2), in stable outpatients with HFpEF. We prospectively analysed data from 133 consecutive stable outpatients who underwent cardiopulmonary exercise testing and echocardiography on the same day. Data were validated in a cohort of HFpEF patients from San Paolo Hospital, Milan, Italy. A multivariable linear regression assessed the association between iLVEDV and peakVO2. The mean age was 73.2 ± 10.5 years, and 75 (56.4%) were women. The median iLVEDV, indexed left ventricular end-systolic volume, and left ventricular ejection fraction were 46 ml/m2 (30-56), 15 ml/m2 (11-19), and 66% (60-74%), respectively. The median peakVO2 and percentage of predicted peakVO2 were 11 ml/kg/min (9-13) and 64.1% (53-74.4), respectively. Adjusted linear regression analysis showed that smaller iLVEDV was associated with lower peakVO2 (p = 0.0001). In the validation cohort, adjusted linear regression analysis showed a consistent pattern: a smaller iLVEDV was associated with a higher likelihood of reduced peakVO2 (p = 0.004). In stable outpatients with HFpEF, a smaller iLVEDV was associated with a lower maximal functional capacity. These findings suggest a need for further studies to understand the pathophysiological mechanisms underlying these observations and to explore targeted treatment strategies for this patient subgroup.

Age, Race, Sex and Cardiorespiratory Fitness: Implications for Prevention and Management of Cardiometabolic Disease in Individuals with Diabetes Mellitus.

Physical inactivity and poor cardiorespiratory fitness (CRF) are strongly associated with type 2 diabetes (DM2) and all-cause and cardiovascular morbidity and mortality. Incorporating physical activity promotion in the management of DM2 has been a pivotal approach modulating the underlying pathophysiology of DM2 of increased insulin resistance, endothelial dysfunction, and abnormal mitochondrial function. Although CRF is considered a modifiable risk factor, certain immutable aspects such as age, race, and gender impact CRF status and is the focus of this review. Results show that diabetes has often been considered a disease of premature aging manifested by early onset of macro and microvascular deterioration with underlying negative impact on CRF and influencing next generation. Certain races such as Native Americans and African Americans show reduced baseline CRF and decreased gain in CRF in randomized trials. Moreover, multiple biological gender differences translate to lower baseline CRF and muted responsivity to exercise in women with increased morbidity and mortality. Although factors such as age, race, and sex may not have major impacts on CRF their influence should be considered with the aim of optimizing precision medicine.

Cardiorespiratory Fitness Is Associated with Decreased Platelet Reactivity.

Platelets are key mediators in cardiovascular disease (CVD). Low cardiorespiratory fitness (CRF) is a risk factor for CVD. The purpose of our study was to assess if CRF associates with platelet function. Platelet assays and cardiopulmonary exercise testing were conducted in the Framingham Heart Study (n = 3,014). Linear mixed effects models estimated associations between CRF (assessed by peak oxygen uptake [VO2]), and multiple platelet reactivity assays. Models were adjusted for multiple medications, risk factors, relatedness and prevalent CVD. Nineteen associations passed the significance threshold in the fully adjusted models, all indicating higher CRF associated with decreased platelet reactivity. Significant traits spanned multiple platelet agonists. Strongest associations were observed in Multiplate whole blood testing after TRAP-6 (e.g., velocity, beta = -0.563, 95% CI [-0.735,-0.391], p = 1.38E-10), ADP (e.g., velocity, beta = -0.514, 95% CI [-0.681,-0348], p = 1.41E-09), collagen (e.g., velocity, beta = -0.387, 95% CI [-0.549,-0.224], p = 3.01E-06), ristocetin (e.g., AUC, beta = -0.365, 95% CI [-0.522,-0.208], p = 5.17E-06) and arachidonic acid stimulation of platelets (e.g., velocity, beta = -0.298, 95% CI [-0.435,-0.162], p = 3.39E-04), and light transmission aggregometry (LTA) after ristocetin stimulation (e.g., max aggregation, beta = -0.362, 95% CI [-0.540,-0.184], p = 6.64E-05). One trait passed significance threshold in the aspirin sub-sample (LTA ristocetin primary slope, beta = -0.733, 95% CI [-1.134,-0.333], p = 3.30E-04), and another in a model including von Willebrand Factor levels as a covariate (U46619, a thromboxane receptor mimetic, AUC in the Optimul assay, beta = -0.36, 95%CI [-0.551,-0.168], p = 2.35E-04). No strong interactions were observed between the associations and sex, age or body mass index in formal interaction analyses. Our findings build on past work that shows CRF to be associated with reduced CVD by suggesting decreased platelet reactivity may play a mechanistic role. We found significant associations with multiple platelet agonists, indicating higher CRF may globally inhibit platelets; however, given multiple strong associations after TRAP-6 and ADP stimulation, PAR-1 and purinergic signaling may be most heavily involved. This is notable since each of these receptor pathways are tied to anti-coagulant (DOACs/thrombin inhibitors) and anti-platelet therapies (P2Y12/PAR1/PAR4 inhibitors) for CVD prevention.

Physical fitness is an independent predictor of chronic kidney disease development in apparently healthy individuals.

The cardiovascular and metabolic benefits of physical activity have been studied at length, however, data on the association between physical fitness and progression to kidney disease is lacking. We aimed to identify the association between cardiorespiratory fitness and development of chronic kidney disease (CKD) among the healthy population. We retrospectively investigated 11,579 healthy self-referred subjects who underwent annual medical screening. All subjects had an estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73 m2, no known kidney disease, hematuria or proteinuria, and were free of diabetes or cardiovascular disease at baseline. All participants completed a maximal exercise test, and were categorized into low and high cardiorespiratory fitness groups based on age- and gender-specific quintiles. The primary end point was the development of significant CKD defined as eGFR below 45 ml/min/1.73 m2 during follow-up. Median follow-up was 7.6 years, and the participants' median age was 50 ± 8 years. Baseline creatinine and eGFR were 1.02 mg/dl and 81 ml/min/1.73 m2, respectively. During follow-up, 81 (0.6%) participants developed CKD, and the cumulative probability was significantly higher among the low fitness group (HR = 2.41, p = 0.001). The effect of physical fitness on the risk to develop CKD remained significant after adjusting for age, gender, baseline creatinine and other cardiovascular risk factors. Cardiorespiratory fitness is an independent risk factor inversely associated with development of CKD.

Association Between Microvascular Disease and Cardiorespiratory Fitness Among Adults With Type 2 Diabetes.

Little is known about the extent to which microvascular disease is associated with cardiorespiratory fitness (CRF) among individuals with type 2 diabetes. A total of 4,766 participants with type 2 diabetes underwent maximal exercise testing in the Look AHEAD (Action for Health in Diabetes) study at baseline. Low CRF was defined based on the Aerobics Center Longitudinal Study reference standards. Microvascular disease was defined as having one or more of diabetes-related kidney disease (DKD), retinopathy, and neuropathy. The burden of microvascular disease was defined as the number of microvascular beds affected. Of the 4,766 participants (mean age 58.9 ± 6.7 years, 58.5% women, 66.1% White individuals), 1,761 (37%) had microvascular disease. Participants with microvascular complications in three vascular territories had a lower CFR than those without any microvascular disease (mean adjusted metabolic equivalent of task [MET] 6.58 vs. 7.26, P = 0.001). Participants with any microvascular disease had higher odds of low CRF than those without microvascular disease (adjusted odds ratio [OR] 1.45, 95% CI 1.24-1.71). An increasing burden of microvascular disease was associated with higher odds of low CRF (for microvascular disease in three vascular territories, adjusted OR 2.82, 95% CI 1.36-5.85). Adjusted ORs for low CRF were 1.24 (95% CI 0.99-1.55), 1.34 (95% CI 1.02-1.76), and 1.44 (95% CI 1.20-1.73) for neuropathy, retinopathy, and DKD associations, respectively. In a large cohort of adults with type 2 diabetes, the presence of microvascular disease and its burden were independently associated with lower CRF.